Introduction and Objective: Septic shock is a highly lethal syndrome initiated by severe, overwhelming infection. This condition is the leading cause of death in Intensive Care Units in the U.S. The underlying mechanisms that cause this syndrome remain incompletely understood despite more than a half century of scientific investigation. These studies seek to examine septic shock pathogenesis and to explore the potential of novel therapeutic strategies using both small and large models of the syndrome, patients with sepsis, and normal volunteers challenged with endotoxin. Proposed Course of Work: Ongoing comparative survival study of commonly used vasopressors in septic shock including epinephrine, norepinephrine and vasopressin. Protocols under development for lymphocyte adoptive transfer, and intra-aortic balloon pump support in septic shock. Investigate the hypothalmic-pituitary-adrenal axis in sepsis and the mechanisms by which low dose glucocorticoid replacement therapy improves survival in septic shock. Validate and apply information on biomarkers and pathogenic pathways obtained from functional genomic investigations.